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Common kidney blood test unsuitable for diagnoses in Africans – large cohort study

Kidney prevalence may be much higher in Africa than previously thought as a commonly used blood test which measures how well a person’s kidneys are working may not pick up kidney disease for people in Africa, meaning that many people could miss early diagnosis and life-saving treatment.

The results of a recent study suggest that kidney disease prevalence in Africa than previously thought has increased from about one in 30 people to about one in eight people.

Kidney disease is silent in the early stages because many people only develop symptoms when their glomerular filtration rate (GFR) drops below 30 to 45 millilitres (ml). This means most people won’t know their GFR is lower than usual, which is why screening people with risk factors for kidney disease remains essential.

Recent research, titled Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study, and published in The Lancet Global Health, is the largest study to analyse kidney disease testing and prevalence on this continent, and the findings suggest that methods developed in high-income settings to check kidney function are not accurate for many people in Africa.

The team from the African Research on Kidney Disease (ARK) Consortium ran the study, which focused on more than 2 500 people in Malawi, South Africa and Uganda.

About the study

Testing how well kidneys function is essential to diagnosing kidney disease in individuals and predicting the burden of kidney disease in populations.

Glomerular filtration rate (GFR) is the most common way to assess kidney function and is a measure of how much blood the kidneys are filtering per minute.

Testing kidney function involves measuring how much creatinine or cystatin C is in a person’s blood.

Creatinine is a by-product of muscle breakdown while cystatin C is a protein made by cells in the body. Healthy kidneys filter creatinine or cystatin C out of the blood and excrete these in urine. A creatinine or cystatin C test thus measures how well kidneys are performing. High levels can be a sign that the kidneys are not functioning properly.

To study the most accurate way to measure kidney function in African populations, the ARK Consortium compared the widely used creatinine and cystatin C-based tests with a benchmark test called the iohexol measured glomerular filtration rate (mGFR).
Iohexol is an iodine-like dye used as a diagnostic contrast agent in CT scans.

The ARK researchers found that creatinine-based tests were inaccurate for predicting kidney disease in African populations.

For example, Africans can have lower creatinine levels due to inadequate nutrition (especially low protein ingestion), short stature and low muscle bulk. Creatinine may also be excreted differently in African populations.

According to the National Kidney Foundation, creatinine is: “A waste product that comes from the normal wear and tear on muscles of the body. Creatinine levels in the blood can vary depending on age and body size. A creatinine level greater than 1.2 for women and greater than 1.4 for men may indicate that the kidneys are not working properly. As kidney disease progresses, the level of creatinine in the blood rises.”

“The equation that is used to test kidney function is wrong for 1.4bn people – Africans,” said co-lead author of the study, Dr June Fabian of the University of the Witwatersrand. “Kidney disease can be debilitating and ultimately fatal if left untreated. Blood tests are useful to spot early signs of kidney problems – and can help identify people who would benefit from treatment.”

She told Health-E News: “We don’t have a lot of funding to do these studies, so a lot of them are often situated in a hospital with many HIV patients. So, they’ll report a high prevalence of chronic kidney disease, but it does not necessarily reflect what’s going on at the community level or in the general population.”

Fabian said population-based studies are required. But these are expensive and need a larger sample group. “This is why there isn’t a lot of data from Africa. In addition, different criteria are used to determine the prevalence of kidney disease in other studies, making available data challenging to interpret.”

The “gold standard” refers to the method to measure kidney function that is currently working to diagnose kidney disease in Africa. Fabian said the problem was that it was expensive and impractical because a person must be there for six hours.

“Because African Americans are big and have a lot of muscle, everyone assumes that everyone else in Africa is the same. Everyone thought that African populations have lots of muscle, and the creatinine would be high as they see it in African Americans. We found that people are quite small.”

Fabian explained that another dependent factor is how much meat a person eats.

“If meat is regularly in your everyday diet, your creatinine will increase. In poorer communities, people often don’t have a lot of money and don’t eat much meat. Even in Bushbuck Ridge, women have very low creatinine, and we’re not sure exactly why. But in Malawi, people might eat meat once every two weeks or once a month. That is not the same as high-income settings where people eat meat almost daily.

“If you’ve got diabetes, and you go and see a primary health care nurse to test your kidneys, she’ll pull a tube of blood, send it to the lab, and the lab will measure the creatinine. And based on that, she’ll work out what we think the kidney function is.”

This is done by estimating the GFR, which is how much blood your kidneys are filtering through per minute. A high GFR means the kidneys are working very well.

“What we realised when we did this study is that kidney function in African populations is overestimated by using the creatinine test. We are reporting GFRs that are too high because these estimation calculations are based on studies done in high-income settings.”

Before the ARK study, Fabian said the studies were done in countries like the US, Sweden, and Belgium. Very few studies have covered the African population looking critically at how kidney disease affects people.

“That is what we wanted to check in this study because a handful of really small studies showed that maybe the way it’s done in Europe doesn’t apply in Africa. This is because we are reading the kidney function as too high. If your GFR is less than 60, your kidneys filter less than 60 ml per minute. If the test pushes everyone up, we are not picking up people with those lower GFRs, which means we’re missing kidney disease.”

These kinds of factors are not considered during studies in high-income settings, she told Health-E News, emphasising the importance of doing this work in African populations.

“The point of our study was to try to standardise all of that. Because we did that, I think we can quite reliably say that the prevalence is between six and 12% depending on the country because people have different risk factors in different countries,” she said.

ARK researchers used the results of their study, along with population data from Burkina Faso, Ghana, Kenya, Malawi, South Africa and Uganda, to estimate overall levels of kidney disease.

The results suggest that kidney disease prevalence may be substantially higher in Africa than previously thought, increasing from about one in 30 people to about one in eight people.

“The results show it is critical to consider whether research into what we consider to be ‘normal’ blood tests applies to all parts of the world,” said senior author Dr Laurie Tomlinson of the London School of Hygiene & Tropical Medicine (LSHTM).

“We have shown that for people living in Africa, differences in factors such as childhood health and current nutrition mean that if we’re using equations developed in the US and Europe, we may not be accurately estimating the kidney function of people globally. The burden of kidney disease in Africa has been substantially underestimated and kidney disease has not received the public health focus it requires.”

Cystatin C test trumps creatinine – but it costs

Tests based on cystatin C worked better than creatinine as an indicator of poor kidney function, but the cystatin C testing is not widely used or available in Africa.

The cystatin C test, which would be more suitable in Africa, costs around R320, significantly more expensive than the widely-used but less accurate creatinine, at just R67.

“We know that cystatin C is better in Africa but relatively speaking it’s a no-go in resource poor settings,” said Fabian.

The findings of the ARK study suggest that switching from the creatinine test of kidney function to cystatin C would be preferable. Ensuring accessibility and enabling doctors to use them should be a priority for Africa, researchers say, and further research for alternative biomarkers is also vital.

“Kidney disease has been neglected across the world but more so in countries in Africa, where it has devastating effects,” said co-lead author Dr Robert Kalyesubula of the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit.

“Our study provides evidence that kidney disease in Africa is much more rampant than previously thought. This is why it is important we continue to engage all stakeholders to ensure access to better diagnostic tests, like cystatin C, to improve early detection and care for patients with kidney disease in Africa.”

Limitations

The ARK Consortium acknowledged limitations in the study, in particular that inaccuracies in the measurement of creatinine or measured GFR could have affected the results. The study population was predominantly people with normal levels of serum creatinine, unlike previous studies into measured kidney function which have included many people with known kidney disease.

Finally, while the study is the largest of its kind from Africa and includes measured GFR from three countries, the diversity of African populations means it is possible that there is greater variability in the relationship between creatinine and measured GFR than the team identified, which could affect the accuracy of the estimates of prevalence of kidney disease in the broader population studies.

Study details

Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study

June Fabian, Robert Kalyesubula, Joseph Mkandawire, Christian Holm Hansen,
Prof Dorothea Nitsch, Eustasius Musenge, et al

Published in The Lancet on 13 July 2022

Summary

Background
The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations.

Methods
We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa.

Findings
Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa.

Interpretation
Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed.

 

The Lancet Global Health article – Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study (Open access)

 

Wits University News article – Widely-used kidney function tests underestimate scale of kidney disease in Africa (Open access)

 

Health-e News article – Study: Kidney function test not suitable for Africans (Open access)

 

See more from MedicalBrief archives:

 

HIV patients at greater risk of both heart and kidney disease

 

Significant variability in capacity for kidney care across the world

 

Hope for HIV/Aids patients with kidney disease

 

Should race be a factor in medical treatment?

 

 

 

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